BDNF val66met influences time to onset of levodopa induced dyskinesia in Parkinson’s disease
- T Foltynie1,2,
- B Cheeran2,
- C H Williams-Gray1,
- M J Edwards2,
- S A Schneider2,
- D Weinberger3,
- J C Rothwell2,
- R A Barker1,
- K P Bhatia2
- 1Cambridge Centre for Brain Repair, Cambridge, UK
- 2Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK
- 3Clinical Brain Disorders Branch, National Institute for Mental Health, Bethesda, Maryland, USA
- Dr T Foltynie, Institute of Neurology, Queen Square, London WC1N 3BG, UK; T.Foltynie{at}ion.ucl.ac.uk
- Received 23 May 2008
- Revised 4 September 2008
- Accepted 11 September 2008
- Published Online First 31 October 2008
Abstract
Background: Levodopa induced dyskinesias (LID) are a common problem which ultimately limit the effective treatment of patients with Parkinson’s disease (PD). There is accumulating evidence that LID develop due to abnormal synaptic plasticity, which is in turn influenced by the release of brain derived neurotrophic factor (BDNF).
Methods: The influence of a common functional polymorphism of the BDNF gene on the risk of developing dyskinesias in a large cohort of patients with PD (n = 315), who were independently and variably treated with levodopa and/or other dopaminergic treatments, was investigated.
Results: Patients with the met allele of BDNF, associated with lower activity dependent secretion of BDNF, were at significantly higher risk of developing dyskinesias earlier in the course of treatment with dopaminergic agents (hazard ratio for each additional met allele 2.12, p = 0.001), which persisted following adjustment for potential confounding variables.
Conclusion: This functional polymorphism may help predict which individuals are most at risk of LID and is consistent with the known actions of BDNF on synaptic plasticity in the striatum.
Footnotes
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See Editorial Commentary, p 129
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T Foltynie and B Cheeran are joint first authors.
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R A Barker and K P Bhatia are joint senior authors.
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Funding: The Wellcome Trust provided financial support to TF through a Clinical Training Fellowship during the collection of the data used in this study.
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Competing interests: None.
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Ethics approval: Ethics approval for the study was granted by the Cambridge Research Ethics committee.
